Our experimental approach utilizes x-ray CT-derived indicator dilution curves. Two projects were completed this part year. Project I: This study evaluates how well the hemodynamic behavior of recruitable and non-recruitable components of the myocardial microvasculature can be quantitated in the intact heart with hole-body CT anesthetized pigs. Sequential injections of a suspension of nonradioactive, 15mm diameter, microspheres into a selected coronary artery. Regional myocardial perfusion (F, ml/g/ min), intramyocardial blood volume (r, ml/g) were estimated from these dynamic CT image sequences. For the intramyocardial microcirculation r=AoF+BoF1/2, where A=0.016 and B=0.076, the local slope of the relationship is an index of the transit time through the intramyocardiaal blood volume. The significance of this study is that the blood volume-to-flow relationship may be quantitative indicator of intramyocardial microvascular functional status. Project II: Anesthetized pigs scans were performed before and during occlusion and at 30 minutes time intervals during reperfusion of a coronary artery that has been occluded for either 0, 15, 30, 60, or 120 minutes. Regional myocardial perfusion (F), intramyocardial blood volume (r) and myocardial microcirculatory permeability-surface area product (PS, ml/g/min) were estimated from these dynamic CT images sequences. With increasing duration of ischemia the PS product remained unchanged (p>.1), but an index of Permeability (PS/r) increased with progressive duration of ischemia (p<.01). The significance of this study is that these studies are supporting the hypothesis that CT-based estimates of microvascular permeability provide a means for detecting for potential ischemia in adequately perfused myocardium.